Fundamentals of Neurogastroenterology: Physiological Aspects and Clinical Implications
Source: Gastroenterology, Accepted Date: 3 February 2026
Topic: Neurogastroenterology - Physiology and Pathophysiology of GI Function and DGBI
Author(s): Houghton LA, De Giorgio R, Boeckxstaens GE, Cryan JF, D'Amato M, Dinning PG, Hasler WL, Vanuytsel T
1. Introduction and Overview
Digestive tract maintains homeostasis and general well-being via complex physiological functions including motility, mixing of ingesta with pancreatic/biliary/enteric secretions, absorption of digested nutrients, and disposal of undigested residues
Processes occur without conscious perception; ~30-40% of general population complain of digestive symptoms, often meal-triggered
Most symptomatic individuals labeled as having disorder of gut-brain interaction (DGBI)
DGBI pathophysiology involves: bidirectional dysregulation of gut-brain axis, microbial dysbiosis, altered mucosal immune function, increased epithelial barrier permeability, visceral hypersensitivity, and abnormal GI motility
2. Peripheral Nerves and Afferent Signaling
GI tract is densely innervated to provide information on luminal contents, potential threats, and normal digestion/absorption processes
Information collected by intrinsic and extrinsic afferent nerves to generate appropriate physiological responses for homeostasis
Sensory neurons of enteric nervous system (ENS) activate local responses
Vagal Afferents
Vast array of receptors expressed on vagal afferents detecting gut hormones, neurotransmitters, stretch, tension, and intestinal molecules (e.g., bacterial metabolites)
Specialized structures on enteroendocrine cells (EECs) called neuropods transduce sensory signals from intestinal milieu to brain via synapse-like connections to afferent nerves including vagus nerve
Vagal afferent cell bodies in nodose ganglion, connecting mainly to nucleus of solitary tract (NTS) and subsequently to dorsal motor nucleus of vagus
Cell bodies in dorsal root ganglia, synapse in spinal cord, send information to brainstem
Primarily act as nociceptors transmitting potentially noxious stimuli
Ascending Pathways and Visceral Pain
Vagal fibers ascending from GI tract synapse bilaterally on NTS; intestinal afferents synapse in subnucleus commisuralis and medialis (intermediate to caudal NTS)
Signaling continues to other brainstem nuclei and forebrain structures; multisynaptic pathways communicate with entire brain
Visceral hyperalgesia to rectal/gastric distension drives mechanistic work in IBS and functional dyspepsia (FD)
Pain sensation mediated by different afferents depending on GI tract region: rectum involves pelvic pathways; proximal pain mediated by thoracolumbar spinal afferents
Inflammation can change response of specific sensory neuron classes and ascending pathway involvement (relevant to post-inflammatory hypersensitivity and post-infection IBS)
Hunger, satiety, fullness, nausea sensations primarily use vagal afferent pathways
Microbiome-Gut-Brain Axis
Gut microbiota (trillions of microorganisms with their genes) key player in moderating signals from gut to brain
Direct relevance to DGBI (Figure 1)
3. Brain Processing
Multiple facets defining conscious experience of pain or sensations shaped in brain: sensory-discriminative, affective-motivational, behavioral-motor, and cognitive components
Nociceptive ascending signals from gut reach brain via anterolateral and dorsal column (spinothalamic tract most important anterolateral pathway)
Spinothalamic projections to ventral and medial thalamus nuclei; connections from ventral nuclei to primary/secondary somatosensory cortex mediate sensory-discriminatory aspects (intensity, duration, location)
Connections between medial thalamus and limbic system (including anterior cingulate cortex - ACC) and midbrain (periaqueductal gray - PAG) shape affective-motivational aspects
Brain imaging studies (fMRI, PET) describe alterations in regional brain activation in DGBI patients (mostly IBS and FD) during visceral stimulation vs. controls
Specific brain functions (pain processing, emotion, cognition) result from dynamic interactions of distributed brain areas in large-scale networks
Effect sizes generally small; causality not demonstrated in longitudinal studies
4. GI Motility: Overview
Motor activity aims to propel and mix luminal contents, increase intestinal absorptive capacity
Provides transient storage in some regions, prevents retrograde movement, facilitates expulsion of residues
Dysmotility develops through gut-brain axis mechanisms: inflammatory/immune/infiltrative/degenerative processes affecting muscle/ENS; indirect trigger via excess stimulation of visceral afferent fibers influencing local motor function via prevertebral ganglia
Visceral afferent activation induces autonomic changes integrated in brainstem (heart rate, colonic tone - e.g., vagally-mediated gastro-colonic motor response increased in DGBI)
Psychosocial stressors induce profound alterations in GI motility
5. Contractile Activity and Tone
Cyclic variations in transmembrane potential of smooth muscle cells occur in stomach, small bowel, colon (recorded as slow-wave activity, electrical control activity, pacesetter potential, or basal electrical rhythm)
Excitatory neurotransmitter (e.g., acetylcholine) depolarizes transmembrane further; when excitation threshold exceeded, electrical spikes occur superimposed on plateau phase of slow-wave activity
Phasic (short-duration) contractions originate from electrical spikes; frequency dictated by slow-wave frequency
Maximum contractile frequency: stomach ~3/min, small intestine declines from ~12/min (duodenum) to 7/min (terminal ileum)
Colon has mixture of slow wave frequencies: 1-12/min; correlation between electrical and contractile activities less clear
Whether phasic contractions accomplish mixing vs. propulsion depends on temporal (frequency, duration) and spatial (spread of propagation) characteristics
Phasic contraction defined as duration not exceeding span of slow-wave cycle; some longer motor events also considered phasic (e.g., "prolonged propagated" or "giant migrating" contractions)
Tone = more prolonged state of contraction, not regulated by slow waves; recognized in proximal stomach (accommodation response to meal), colon (response to feeding), and sphincteric regions
Tone regulated by actin-myosin interaction via cellular mechanisms modulated by neurogenic and mechanical stimuli
Phasic contractions may be superimposed on tonic activity; tone modifies wall tension in response to gut filling, determining perception of distension
6. Compliance and Related Phenomena
Compliance = capability of gut region to adapt to intraluminal distension, expressed as ratio of change in volume to change in pressure (dV/dP) from pressure-volume curve
Contributing factors: organ capacity (diameter), elastic properties of gut wall (thickness, fibrotic component, muscular activity), elasticity of surrounding organs (influenced by fibrosis, ascites, abdominal masses)
Distending intraluminal volume produces stretch and tension (force) on gut wall, determining intraluminal pressure increment
Wall tension, intraluminal pressure, volume interrelated by Laplace's law: Tension (T) = Pressure (P) x Radius (R)/2 for sphere; T = P x R for cylinder
Equation influenced by compliance: contracted gut (tone increases) produces greater wall tension and higher intraluminal pressure for same volume
Perception of gut distension partly determined by wall tension, not just volume or pressure; assessment of wall tension important in interpreting visceral stimulus perception tests
7. Transit
Flow = local movements of intraluminal content; transit = time for food/material to traverse specified GI region
Transit is most important motility aspect in clinical terms, representing net interaction of other parameters and relevant index of organ function
Most measurements based on detecting intraluminal movements of extrinsic marker labeling luminal content
Transit depends on: physical (solid, liquid, gas) and chemical (pH, osmolality, nutrient composition) nature of gut contents and marker; state of motility at time of marker administration (fasted vs. fed); gut preparation
Common measurements: half time for emptying (t1/2) for stomach/colon, amount (%) emptied at given time after administration
Esophageal transit time: ~2-5 seconds for bolus head
Gastric t1/2 for light meal: usually <90 minutes
Small intestinal transit: head of meal reaches cecum within 120 minutes
Colonic normal half-emptying time: ~48 hours (wide variability)
Relationship between transit and phasic activity or tone incompletely understood; radiolabeled colonic contents in healthy subjects show only 28% associated with propagating sequences (32% nonpropagating, 40% no pressure events)
Patients with chronic constipation and normal transit can exhibit reduced fasting and/or postprandial colonic tone
8. Factors Influencing GI Physiology
Immune Activation and Inflammation
Interest in immune cell infiltration in DGBI increased after observation that mononuclear cells and T lymphocytes remain elevated in rectal biopsies of patients who developed post-infection IBS (PI-IBS)
Subsequent studies reported conflicting data on elevated lymphocyte numbers in DGBI biopsies; extent to which increased T cells generate symptoms remains unclear
Barbara et al. milestone paper showed increased mast cell counts localized close to nerve fibers in IBS; several studies confirmed this finding in all IBS subtypes, mainly left hemicolon
This finding is disputed by studies showing no increase or even decrease in mast cell numbers
In FD, evidence for mast cells is limited; more directed towards eosinophils
Initial reports suggested duodenal eosinophilia as feature of postprandial distress syndrome (PDS), but recent meta-analysis showed similar counts in different FD subgroups
Literature on increased lymphocytes, mast cells, eosinophils in DGBI controversial due to differences in patient selection, geographic differences, or quantification methodology
Activation status and mediator release may be more important than immune cell numbers
Approach to assess activation: measure cytokine expression in biopsies or circulating cytokines
Larger IBS studies identified "immune-active" phenotype in 1/5 to 1/3 of patients with higher expression levels of IL-1β and prostaglandin synthase 2
Most convincing evidence for immune activation: studies evaluating bioactive mediators released by biopsies
IBS supernatant contains more histamine and tryptase vs. controls, activates murine visceral afferents or human submucosal neurons (blocked by histamine antagonists and serine protease inhibitors)
Intestinal epithelial cells of IBS patients release increased levels of active protease trypsin-3, signaling to enteric neurons and inducing visceral hypersensitivity
Increased levels of TRPV4 agonist, 5,6-epoxyeicosatrienoic acid (polyunsaturated fatty acid metabolite) reported in IBS biopsies
Evidence for altered synthesis/release of pro-nociceptive mediators in FD limited; increased spontaneous release of histamine and serotonin by gastric biopsies reported in post-infection FD (PI-FD)
Barrier Dysfunction
First report in 2000; several groups reported increased small intestinal and colonic permeability in IBS using various techniques
Impaired barrier function most consistently shown in PI-IBS and diarrhea-predominant IBS (IBS-D)
In constipation-predominant IBS (IBS-C), majority of studies showed no difference with healthy controls
Colonic mucosa permeability measured in Ussing chambers increased in IBS as group
In majority of studies, permeability measures correlated to stool pattern or pain severity; association absent or inverse in other reports
Causal evidence linking increased permeability to symptoms and visceral hypersensitivity still lacking
Observed barrier defect transferable by colonic infusion of fecal water from IBS patients in mice or by incubating cell lines with biopsy supernatant (role for luminal mediators)
Smaller number of studies evaluated permeability in FD: higher permeability demonstrated in vitro and in vivo
Most studies showed no association between intestinal permeability and symptom severity
Expression of several tight junction related proteins altered in different GI regions in IBS and FD; reported abnormalities and link to symptoms not consistent between studies
Etiology of barrier defect in DGBI unclear; luminal mediators (proteases, bile acids), psychological stress, immune activation, decreased glutamine all implicated
Psychological Factors and Stress
Acute or chronic stress disrupts normal homeostasis due to actual or perceived threat
Data on effect of stress on GI physiology in humans limited; most knowledge from animal studies
Delayed gastric emptying but similar accommodation response observed after acute stressor in healthy individuals
In FD patients, state anxiety and comorbid anxiety disorders associated with impaired accommodation
History of physical abuse associated with delayed gastric emptying
Duodeno-jejunal contractions suppressed during acute psychological stress
Colonic contractions stimulated by artificial stressor in IBS patients but not healthy individuals
Exogenous corticotropin-releasing hormone (CRH) reproduced enhanced colonic motility in male IBS patients
Exogenous CRH also stimulated esophageal contractility in healthy controls
Stress impairs intestinal barrier function through mast cell-dependent mechanism
Overexpression of CRH by intestinal eosinophils correlated with background life stress and clinical severity in IBS-D patients
Visceral sensitivity enhanced during states of psychological stress: reported for esophageal acid perfusion, colonic distension, anorectal electrostimulation
Exogenous CRH enhanced esophageal sensitivity to distension in healthy individuals
History of sexual and physical abuse associated with lower discomfort threshold during gastric distension in FD patients
Food and Meal Intake
Once food reaches stomach, tension-sensitive mechanoreceptors engaged, send gastric filling-related satiation signals to brainstem via vagal afferents
Hormone leptin involved in these processes
Peristaltic contractions in stomach advance fragmented meal components into duodenum where mucosal EECs sense nutrient composition
This activates negative feedback system enhancing gastric accommodation and slowing gastric emptying rate
Duodenal EECs respond to nutrient exposure by releasing key peptides: glucagon-like peptide-1 (GLP-1) or cholecystokinin (CCK)
These peptides activate vagal afferents or enter circulation
GLP-1 infusion at physiological levels delays gastric emptying, results in increased satiety (important anorexigenic hormone and therapeutic target in obesity)
Ghrelin and motilin are two key peptides involved in hunger signaling
Increases in circulating ghrelin following food restriction signal increase in appetite/hunger, correlated with increased "liking" and "wanting" of food
Return of hunger driven by motilin release, triggering complex contractility pattern simultaneous with hunger peak (mechanisms controlling motilin release poorly understood)
From clinical DGBI perspective, food intake often associated with symptom occurrence
In FD patients, gastric accommodation impaired in subset, associated with early satiation and weight loss
Dietary FODMAPs (fermentable oligo-, di-, monosaccharides and polyols) exclusion offers relief in subset of IBS patients
FODMAPs influence drop in intragastric pressure during food intake and subsequent rise; size of gastric accommodation may respond to meal nutrient composition, involved in triggering meal-induced symptoms
Microbiome
Bidirectional communication along microbiome-gut-brain axis fundamental to synergy between GI microbiome and host (Figure 1)
Gut microbiota-brain axis increasingly received attention for role in pathophysiology of many DGBI disorders including IBS (characterized by visceral pain)
Emphasis on role of microbiota in pain responses, particularly visceral pain
Studies in male germ-free mice (lacking gut-microbiota from birth) showed increased visceral hypersensitivity to colorectal distension, reduced following microbial colonization
Modulation of gut microbiota in rodents using antibiotics in early life induces visceral pain
Manipulation of gut microbiota using probiotic bacterial species (Bifidobacterium, Lactobacillus, Streptococcus strains) and their soluble mediators reduces visceral pain response
Bacterial production of histamine may underpin visceral pain in animal models and small subgroup of IBS patients
Microbes communicate via metabolites similar to those recognized by host cells, interacting with intestinal epithelium
Neuromodulatory compounds include tryptophan precursors and metabolites: 5-hydroxytryptamine (5-HT), gamma-aminobobutric acid (GABA), catecholamines
Studies involving germ-free mice show brain affected by absence of microbiota
Animals orally-gavaged with specific bacterial strains demonstrated alterations in behavior
Human studies involving similar bacterial strains confirmed potential translatability of findings
Accumulating clinical evidence in DGBI that there may be microbiome-based signature in IBS
Increasing numbers of meta-analyses show certain probiotic bacterial strains may offer benefit in IBS
Pilot study in IBS patients showed probiotic Bifidobacterium longum NCC3001 reduces depression by reducing limbic reactivity in brain
Exact mechanism underpinning contribution of microbiome to DGBIs requires more attention
Fecal microbiota transplants being studied clinically, results so far inconclusive
Genetics and Epigenetics
Gene-hunting efforts in IBS mostly limited to candidate gene surveys; Genome-Wide Association Studies (GWAS) only recently reported in international large-scale population-based biobanks
Compelling evidence for IBS-predisposing role provided for sucrase-isomaltase gene SI, coding for brush border enzyme breaking down carbohydrates like sucrose and starch
By analogy with congenital sucrase-isomaltase deficiency (CSID): i) adult CSID cases can be misdiagnosed as IBS-D; ii) defective SI variants increase IBS risk; iii) SI carriers less likely to benefit from low-FODMAP diet
Evidence highlights role of food triggers in IBS, provides rationale for personalizing (dietary) therapeutic approaches in SI genotyped patients
Following early population-based pilot studies, few large-scale GWAS reported for IBS and its endophenotypes (gut motility studied as number of bowel movements via questionnaire data)
GWAS led to identification of genes previously associated with mood and anxiety disorders, expressed in CNS and ENS, and neuropeptide/neurotransmitter signaling pathways
May explain increased prevalence of mental health conditions in IBS and possibly observed efficacy of psychotropic drugs and behavioral therapies
9. Esophagus: Physiology
Esophageal Motility and Function of the Esophagogastric Junction
Main function: propulsion of ingested bolus from oral cavity to stomach through peristaltic contraction
Contraction
9. Esophagus: Physiology (continued)
Proximal striated muscle fibers contraction follows pharyngeal phase of deglutition, directly controlled by sequential activation of somatic motor fibers originating in nucleus ambiguus and nucleus retrofacialis, reaching esophagus via recurrent laryngeal branches of vagus nerve
Distal part of esophagus (predominantly smooth muscle): peristaltic contraction orchestrated by myenteric plexus combined with central input from vagus
Extrinsic innervation of distal esophagus supplied by neurons from dorsal motor nucleus of vagus, synapsing in ganglia of myenteric plexus (not directly innervating motor endplates as in proximal esophagus)
In myenteric plexus, gradient along length of esophagus with progressive increase of inhibitory motor neurons from proximal to distal
Time to contraction determined by intrinsic latency gradient, longer in distal esophagus due to predominantly inhibitory motor neurons
Progressive increase in density of inhibitory neurons with ensuing prolongation of latency to contractions from proximal to distal contributes to esophageal peristalsis
Contraction of longitudinal muscle layer results in shortening with concentration of circular muscle fibers orally to bolus, maximizing contractile strength
Esophagogastric Junction (EGJ)
Consists of superimposed lower esophageal sphincter (LES) and crural diaphragm
Prevents reflux of gastric contents into esophagus by tonic contraction, while allowing passage of swallowed bolus by deglutitive inhibition
Tone largely myogenic but modulated by neuronal input
Upon swallowing or esophageal distension, release of nitric oxide by inhibitory neurons results in active relaxation of EGJ
EGJ can also relax as result of increased pressure in stomach in vago-vagal reflex triggering transient LES relaxation (TLESR)
TLESR is normal phenomenon in healthy individuals allowing gastric belching, but also main mechanism of gastro-esophageal reflux disease (GERD), involved in vomiting and rumination
Sensation
Vagal afferents innervating smooth muscle layer and serosa sensitive to pressure and stretch
Mucosal vagal afferents triggered by various stimuli: chemical (acid, bile), thermal, mechanical from lumen
Vagal afferents not involved in visceral pain transmission to brain; convey physiological stimuli
Spinal afferents have cell bodies in dorsal root ganglia, synapse in dorsal column nuclei, predominantly act as nociceptors transmitting (potentially) noxious stimuli to brain
10. Esophagus: Main Symptoms and Pathophysiology
Symptoms
Dysphagia: subjective sensation of difficult or slow bolus passage, or feeling food bolus gets stuck in chest after swallowing
Organic lesions (strictures, carcinoma): dysphagia for solids precedes dysphagia for liquids, variable progression over time
Motility disorders: dysphagia for solids and liquids typically co-exist from onset (solids cause more pronounced symptoms)
Heartburn: burning-type sensation in retrosternal area, usually starts in upper epigastrium or lower chest region, typically rises behind breastbone toward neck
Most typical symptom of GERD
Intermittent, often triggered by meal, exercise, or while lying down
Can occur in absence of pathological reflux due to esophageal or central hypersensitivity
Chest pain: from esophageal/central origin or non-cardiac chest pain differentiates from heartburn by absence of burning quality, usually manifests as pressure or sharp pain
Most common cause from esophageal origin: GERD
May also result from motility disorders (achalasia, esophageal hypercontractility)
Belching: retrograde movement of air through esophagus followed by eructation
Excessive air in stomach triggers TLESR followed by gastric belching as physiological venting mechanism
Most common mechanism in bothersome, repetitive belching: supragastric belching where air drawn/injected into esophagus and released immediately without reaching stomach
Regurgitation: retrograde movement of gastric contents into pharynx
Typical symptom of GERD
Can also result from rumination where gastric contents pushed back into esophagus by sudden increase in intra-abdominal pressure through contraction of abdominal wall
Effortless regurgitation of recently ingested, pleasantly tasting food in absence of retching or nausea raises suspicion of rumination
Pathophysiology
Esophageal Dysmotility: significant abnormalities detected by manometry exclude DGBI, lead to diagnosis of motility disorder (Chicago Classification v4.0)
Muscle contractions may provoke symptoms: sustained contractions of longitudinal muscle layer (not detected with manometry) closely associated with heartburn and esophageal pain sensation
Hypersensitivity: visceral hypersensitivity well-described in esophageal conditions including non-cardiac chest pain, globus, subtypes of GERD
Multimodal phenomenon: mechanosensitivity to distension, chemosensitivity to luminal substances (acid), thermosensitivity
Can be peripheral, central, or combination
Dysfunction of Upper Esophageal Sphincter (UES): abnormalities including elevated resting pressure and post-swallow residual pressure described in patients with globus sensation
Debate whether causal to symptom generation or consequence of tension/anxiety
Study supporting disease mechanism: globus sensation in 1/3 of healthy volunteers treated with intravenous citalopram, associated with higher post-swallow residual pressure
11. Stomach: Physiology
Gastric Emptying
Depends on meal characteristics
Digestible solid emptying exhibits initial lag phase (depends on size and caloric load), followed by linear phases emptying >90% of meal after 4 hours at 1-4 kcal/minute
Indigestible solids >7 mm occur later upon resuming fasting antral contractions
Emptying of water faster: 50% emptying over <18 minutes
Nutritive liquids emptied slower
Ghrelin and motilin regulate gastric motility, emptying, hunger, satiety
CCK antagonists accelerate gastric emptying (reflecting inhibitory actions of CCK)
GLP-1 agonists slow emptying, while antagonists accelerate emptying
Regional Specific Gastric Motor Patterns
Proximal stomach (fundus, proximal corpus): main response to eating is accommodation - decrease in tone and increase in volume creating storage reservoir
Begins with receptive relaxation upon oropharyngeal or gastric stimulation followed by adaptive gastric relaxation, peaking 15 minutes after eating, mediated by vasovagal reflexes
Proximal tone then increases with gradual food transfer to antrum
Frequency and directionality coordinated by rhythmic electrical oscillations (slow waves) at frequency of 3 cycles per minute initiated by gastric corpus pacemaker interstitial cells of Cajal (ICCs) (Figure 3)
Phasic contractions elicited when action potentials exceed contractile thresholds
Fasting contractility part of migrating motor complex (MMC), recurs every 84-122 minutes
5-10 minute period of regular intense contractions (Phase III) clears stomach of residual undigested residue
Meals suppress MMCs, elicit 2-4 hour fed pattern of irregular contractions (neurohormonal triggers less well understood)
Pylorus: generates both tonic and phasic contractility
Mostly open during phase III, closed for much of fed period
After eating, distally propagating contractions in corpus promote pyloric closure causing food trapping followed by retropulsion into proximal regions for further trituration
Antegrade-retrograde movement increases with higher calorie density meals
Brief pyloric relaxations permit evacuation of small, ground particles into duodenum
Ultrasound shows common antro-pyloro-duodenal channel during transpyloric flow
Vagal afferents activated by distension project to NTS and area postrema with subsequent forebrain and midbrain activation controlling food intake
12. Stomach: Main Symptoms and Pathophysiology
Symptoms of Gastric Dysfunction
Nausea: sensation of impending need to vomit; vomiting = oral expulsion of stomach contents
Defining symptom of chronic nausea vomiting syndrome (CNVS)
Nearly universally reported with gastroparesis
Vomiting requisite for cyclic vomiting syndrome (CVS) and cannabinoid hyperemesis syndrome (CHS), common in CNVS and gastroparesis
Early satiety and postprandial fullness: sense of feeling full before meal completion, sensation of being full for long period (many hours) after normal meal
Reported with PDS subtype of FD and gastroparesis
In gastroparesis, associated with reductions in body mass index
Anorexia: loss of appetite, occurs in FD, gastroparesis, organic conditions
Bloating and distension: distinct clinical features
Bloating = sensation of fullness, excessive gas, or feeling of being distended without obvious abdominal distension
Distension = visible objective enlargement of abdominal girth
Frequently coexist but can occur independently
Commonly reported in PDS and gastroparesis
Epigastric pain: painful sensation located in epigastrium, often described as burning
Defining symptom in epigastric pain syndrome (EPS) subtype of FD
Severe epigastric pain predominant in 20% of gastroparesis patients
Pathophysiology
Delayed Gastric Emptying: gastric emptying testing confers diagnosis of gastroparesis in setting of characteristic gastric symptoms
Only 25-36% of patients with suspected gastroparesis exhibit delayed emptying
Group without delayed emptying given alternate diagnoses including CNVS
One third of FD patients have emptying delays
Importance of delayed gastric emptying for symptom generation controversial:
Most studies report poor gastroparesis symptom correlation with delayed emptying of low-fat meals
Delayed emptying of high fat meals associated with greater nausea, vomiting, fullness, early satiety